Ophthalmic compositions

Abstract

The invention is generally related to artificial tear composition for ophthalmic drug delivery, and more specifically to galactomannan, a cis-diol, a buffering agent and the composition is substantially free of a borate. The ophthalmic formulation having an osmolality in the range between 240 mOsm/kg and to 110 mOsm/kg.

What is claimed is: 
     
         1 . An ophthalmic composition comprising a galactomannan, a buffering agent, and a cis-diol, wherein said formulation is substantially free of borate and wherein said galactomannan is present at a concentration of 0.16 w/v % to 0.19 w/v % and said buffering agent is present at a concentration of 0.1 w/v % to 0.2 w/v %, and wherein said cis-diol is sorbitol at a concentration of 0.5 to 5.0 w/v %, and wherein said galactomannan is selected from the group consisting of guar, hydroxylpropyl guar, and combinations thereof, wherein the buffering agent includes an bis-aminopolyol of formula (I) or a salt thereof 
       
         
           
           
               
               
           
         
         wherein a, b, c, d, e, f, g, and h are independently an integer from 1 to 6; and R and R′ are independently selected from the group consisting of —H, —CH 3 , —(CH 2 ) 2-6 —H, and —(CH 2 ) 1-6 —OH; wherein the ophthalmic formulation having an osmolality in the range between 240 mOsm/kg and to 110 mOsm/kg. 
       
     
     
         2 . The ophthalmic composition of  claim 1 , wherein the bis-aminopolyol is 1,3 bis(tris[hydroxymethyl]methylamino)propane (bis-TRIS-propane). 
     
     
         3 . The ophthalmic composition of  claim 1 , wherein the composition has a pH value between 6.5 to 8.5. 
     
     
         4 . The ophthalmic composition according to  claim 1 , wherein the ophthalmic composition comprises at least one demulcent selected from the group consisting of glycerin, polyvinyl pyrrolidone, polyethylene oxide, polyethylene glycol, polyethyleoxide-polybutyleneoxide block copolymer, polyethyleneoxide-polypropyleneoxide block copolymer, propylene glycol, polyacrylic acid, and combinations thereof. 
     
     
         5 . The ophthalmic composition of  claim 4 , wherein said at least one demulcent is propylene glycol and polyethylene glycol 400. 
     
     
         6 . The ophthalmic composition according to  claim 1 , wherein sorbitol at a concentration of 1.4 w/v %. 
     
     
         7 . The ophthalmic composition according to  claim 2 , wherein the bis-aminopolyol is 1,3 bis(tris[hydroxymethyl]methylamino)propane (bis-TRIS-propane) at a concentration of 0.14 w/v %. 
     
     
         8 . The ophthalmic composition according to  claim 1 , wherein the galactomannan is hydroxylpropyl guar. 
     
     
         9 . The ophthalmic composition according to  claim 1 , wherein the ophthalmic formulation having an osmolality in the range between 220 mOsm/kg and to 170 mOsm/kg. 
     
     
         10 . The ophthalmic composition according to  claim 1 , wherein the ophthalmic formulation having an osmolality in the range between 215 mOsm/kg and to 190 mOsm/kg 
     
     
         11 . The ophthalmic composition according to  claim 1 , wherein the ophthalmic composition comprises an anesthetic drug, a glaucoma therapeutics, a pain reliever, an anti-hypertensive agent, a neuro-protective agent, muco-secretagogue, an angiostatic agent, an anti-angiogenesis agent, a growth factor, an immunosuppressant agent, an anesthetic drug, an anti-infective agent, an antiviral agent, an anti-inflammatory agent, an anti-angiogenesis agent, an anti-myopia agent, an anti-allergy agent, a dopaminergic antagonist, a protein, an anti-microbial, or combinations. 
     
     
         12 . The ophthalmic composition according to  claim 1 , wherein the ophthalmic composition comprises a cooling agent, an antioxidant, a nutriceutical, or combinations thereof. 
     
     
         13 . The ophthalmic composition according to  claim 1 , wherein the ophthalmic composition comprises omega-3 fatty acid, omega-6 fatty acid, vitamin A, vitamin D, vitamin E, tocopherols, vitamin K, beta-carotene, or combinations thereof. 
     
     
         14 . The ophthalmic composition according to  claim 1 , wherein the ophthalmic composition comprises less than 0.1% W/V of borate. 
     
     
         15 . The ophthalmic composition according to  claim 1 , wherein the ophthalmic composition comprises no preservative. 
     
     
         16 . An ophthalmic emulsion, the emulsion comprising:
 water forming an aqueous phase;   oil forming an oil phase;   a hydrophilic surfactant having an HLB value of from 10 to 18;   a hydrophobic surfactant having an HLB value of from 1 to 6;   a charged phospholipid;   a mucoadhesive galactomannan polymer;   a cis-diol; and   an bis-aminopolyol of formula (I) or a salt thereof,   
       
         
           
           
               
               
           
         
         wherein a, b, c, d, e, f, g, and h are independently an integer from 1 to 6; and R and R′ are independently selected from the group consisting of —H, —CH 3 , —(CH 2 ) 2-6 —H, and —(CH 2 ) 1-6 —OH; wherein said formulation is substantially free of borate, wherein the ophthalmic formulation having an osmolality in the range between 240 mOsm/kg and to 110 mOsm/kg. 
         wherein:
 i. the oil phase is in droplets within the aqueous phase and the droplets have an average diameter that is no greater than about 1000 nm, but is at least 10 nm, wherein the average diameter is corresponding to 90% of the cumulative undersize distribution by volume measured using a Microtrac S3500 Particle Size Analyzer (Software Version 10.3.1); and 
 ii. the borate and galactomannan polymer cooperatively act to form a gel upon instillation of the emulsion in an eye of an individual.